We have shown previously that hyperinsulinemia is a key factor in bringing about the many and similar metabolic abnormalities (liver-muscle-adipose) of genetic and experimentally-produced (e.g., hypothalamic lesions) obesities of rats and mice. The central nervous system (CNS) origin of hyperinsulinemia is obvious in hypothalamic obesities. Considerable indirect evidence suggests that such may be the case for genetic obesities. We shall therefore attempt to define : 1) the normal relationships between the CNS (the hypothalamus in particular) and the secretion of insulin and of other pancreatic homones; 2) the possible existence of abnormalities in such relationships, in hypothalamic- and genetic-obese animals. Specifically, we shall study (in normal and obese animals): a) the cephalic phase reflex insulin secretion (a model selected due to its obvious CNS relationship); b) the neural afferents and efferents (by electrophysiological means) of such cephalic insulin secretion. We shall also determine, in normal and obese animals, the pattern of secretion of the pancreatic hormones as well as the routes (neural, humoral) by which the CNS may relate to the endocrine pancreas. The methods used will include hormone secretion in vivo in anesthetized or freely-moving animals; in vivo hormone secretion following acute vagotomy or vagus nerve stimulation; in vitro secretion using isolated perfused pancreases or isolated perifused pancreatic islets.